Hepatitis refers to a variety of conditions that involve inflammation of the liver. Viral hepatitis, of which there are several types (e.g., hepatitis A, B, C, D, and E), is an inflammation of the liver due to a viral infection. Each type of viral hepatitis may exhibit different symptoms and may be characterized by different approaches to treatment and prevention. For example, vaccines have been developed for hepatitis A and B, but not for hepatitis C or E.
The main goal of treatment of chronic hepatitis C is to eliminate detectable viral RNA from the blood. Patients lacking detectable hepatitis C virus RNA in the blood 24 weeks after completing therapy typically have a favorable prognosis and may be considered to be cured of the virus. Such a condition is known as a sustained virologic response. For patients not achieving a sustained virologic response, there may be other more subtle benefits of treatment, such as slowing the progression of liver scarring (fibrosis).
Treatment of hepatitis C virus (HCV) commonly involves administration of injectable interferon (or injectable pegylated interferon), ribavirin, or a combination thereof. Interferon alpha is a naturally occurring glycoprotein that is secreted by cells in response to viral infections. It exerts its effects by binding to a membrane receptor. Receptor binding initiates a series of intracellular signaling events that ultimately leads to enhanced expression of certain genes. This leads to the enhancement and induction of certain cellular activities including augmentation of target cell killing by lymphocytes and inhibition of virus replication in infected cells. Ribavirin is a synthetic nucleoside that has activity against a broad spectrum of viruses.
Interferon alpha, with or without ribavirin, is associated with may side effects. Flu-like symptoms, depression, rashes, other unusual reactions and abnormal blood counts are common examples of such side effects. Ribavirin is associated with a significant risk of abnormal fetal development. Accordingly, women who are potentially pregnant should not begin therapy until a report of a negative pregnancy test has been obtained. Female patients are advised to avoid becoming pregnant during treatment. Patients using interferon alpha and ribavirin are advised to have blood tests approximately once a month, and somewhat more frequently at the beginning of treatment. Certain groups of patients cannot take ribavirin, for example those with anemia, heart disease or kidney disease. In such cases, pegylated interferon alpha is typically prescribed alone. Some patients with hepatitis C (e.g., patients also having advanced liver disease) are advised not to take interferon alpha or pegylated interferon alpha because of the risk of serious side effects. For such patients, no previously available method of treatment is recognized as being effective and safe for treating hepatitis C.
There is therefore a need in the art to develop an effective method of treatment of hepatitis C. An ideal method of treatment would achieve a sustained virologic response in a wide range of patients. Such a treatment would employ readily available active agents and would have minimal side effects. When co-administration of interferon alpha is employed, an ideal method of treatment would require reduced amounts of interferon alpha (i.e., reduced frequency of administration, reduced amount per administration, or both) as compared with traditional methods of treatment.